Supplementing Limosilactobacillus reuteri FN041 alleviates hypercholesterolemia via promoting indole-3-carboxaldehyde production by gut microbiota in high-fat diet mice

Abstract

This study explored how breast milk-derived Limosilactobacillus reuteri FN041 regulates lipid metabolism. C57BL/6N mice on a high-fat diet were treated with FN041, Lacticaseibacillus rhamnosus GG, indole-3-carboxaldehyde, or lovastatin (Lova). Low-fat diet-fed mice and those treated with FN041 served as controls. An oral glucose tolerance test was conducted at week 7, with the experiment concluding at week 8. Results showed that all treatments significantly reduced weight gain rate (p < 0.01) and inhibited increases in plasma total cholesterol, low-density lipoprotein cholesterol, hepatic lipid droplet area, and white adipose tissue area (p < 0.05). Only FN041 significantly decreased body fat percentage (p < 0.05). Mechanistically, treatments attenuated high-fat-induced increases in intestinal permeability and plasma levels of lipopolysaccharide, IL-6, and TNF-α (p < 0.01) while enhancing expression of intestinal Claudin-1 and Occludin. FN041 and Lova increased cecal microbiota richness (Chao1 and ACE indices) and altered β-diversity (PERMANOVA). FN041 specifically upregulated lipid metabolism-regulating bacteria (e.g., Marvinbryantia formatexigens, Bacteroides acidifaciens) and reduced the abundance of Lactobacillus johnsonii and Ligilactobacillus murinus. It also altered cecal and plasma metabolite profiles, increasing levels of cecal indole-3-carboxaldehyde, plsama indole-3-butyric acid, and plsama 5,6-dihydroxyindole-2-carboxylic acid. In summary, FN041 mitigated high-fat-induced weight gain and lipid disorders by enriching beneficial gut bacteria and producing indole derivatives.